Eukaryotic RNA Polymerases: the many ways to transcribe a gene

In eukaryotic cells, three nuclear RNA polymerases (RNA pols) carry out the transcription from DNA to RNA, and they all seem to have evolved from a single enzyme present in the common ancestor with archaea. The multiplicity of eukaryotic RNA pols allows each one to remain specialized in the synthesis of a subset of transcripts, which are different in the function, length, cell abundance, diversity, and promoter organization of the corresponding genes. We hypothesize that this specialization of RNA pols has conditioned the evolution of the regulatory mechanisms used to transcribe each gene subset to cope with environmental changes. We herein present the example of the homeostatic regulation of transcript levels versus changes in cell volume. We propose that the diversity and instability of messenger RNAs, transcribed by RNA polymerase II, have conditioned the appearance of regulatory mechanisms based on different gene promoter strength and mRNA stability. However, for the regulation of ribosomal RNA levels, which are very stable and transcribed mainly by RNA polymerase I from only one promoter, different mechanisms act based on gene copy variation, and a much simpler regulation of the synthesis rate

Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast

The adjustment of transcription and translation rates to the changing needs of cells is of utmost importance for their fitness and survival. We have previously shown that the global transcription rate for RNA polymerase II in budding yeast Saccharomyces cerevisiae is regulated in relation to cell volume. Total mRNA concentration is constant with cell volume since global RNApol II-dependent nascent transcription rate (nTR) also keeps constant but mRNA stability increases with cell size. In this paper, we focus on the case of rRNA and RNA polymerase I. Contrarily to that found for RNA pol II, we detected that RNA polymerase I nTR increases proportionally to genome copies and cell size in polyploid cells. In haploid mutant cells with larger cell sizes, the rDNA repeat copy number rises. By combining mathematical modeling and experimental work with the large-size cln3 strain, we observed that the increasing repeat copy number is based on a feedback mechanism in which Sir2 histone deacetylase homeostatically controls the amplification of rDNA repeats in a volume-dependent manner. This amplification is paralleled with an increase in rRNA nTR, which indicates a control of the RNA pol I synthesis rate by cell volume

A feedback mechanism controls rDNA copy number evolution in yeast independently of natural selection

Ribosomal DNA (rDNA) is the genetic loci that encodes rRNA in eukaryotes. It is typically arranged as tandem repeats that vary in copy number within the same species. We have recently shown that rDNA repeats copy number in the yeast Saccharomyces cerevisiae is controlled by cell volume via a feedback circuit that senses cell volume by means of the concentration of the free upstream activator factor (UAF). The UAF strongly binds the rDNA gene promoter, but is also able to repress SIR2 deacetylase gene transcription that, in turn, represses rDNA amplification. In this way, the cells with a smaller DNA copy number than what is optimal evolve to increase that copy number until they reach a number that sequestrates free UAF and provokes SIR2 derepression that, in turn, blocks rDNA amplification. Here we propose a mathematical model to show that this evolutionary process can amplify rDNA repeats independently of the selective advantage of yeast cells having bigger or smaller rDNA copy numbers. We test several variants of this process and show that it can explain the observed experimental results independently of natural selection. These results predict that an autoregulated feedback circuit may, in some instances, drive to non Darwinian deterministic evolution for a limited time period

Earliest Porotic Hyperostosis on a 1.5-Million-year-old Hominin, olduvai gorge, Tanzania.

Meat-eating was an important factor affecting early hominin brain expansion, social organization and geographic movement. Stone tool butchery marks on ungulate fossils in several African archaeological assemblages demonstrate a significant level of carnivory by Pleistocene hominins, but the discovery at Olduvai Gorge of a child's pathological cranial fragments indicates that some hominins probably experienced scarcity of animal foods during various stages of their life histories. The child's parietal fragments, excavated from 1.5-million-year-old sediments, show porotic hyperostosis, a pathology associated with anemia. Nutritional deficiencies, including anemia, are most common at weaning, when children lose passive immunity received through their mothers' milk. Our results suggest, alternatively, that (1) the developmentally disruptive potential of weaning reached far beyond sedentary Holocene food-producing societies and into the early Pleistocene, or that (2) a hominin mother's meat-deficient diet negatively altered the nutritional content of her breast milk to the extent that her nursing child ultimately died from malnourishment. Either way, this discovery highlights that by at least 1.5 million years ago early human physiology was already adapted to a diet that included the regular consumption of meat

Diversidad afectivo-sexual en mujeres adultas: Una realidad invisibilizada.

La invisibilidad social y científca de la diversidad sexual en mujeres adultas, así como el reduccionismo a la hora de entenderla, nos ha llevado a realizar un estudio con 523 mujeres adultas, con una edad media de 38,52 años (DT = 6,83), de las cuales el 89,3% se consideraba heterosexual. Se evaluaron tres dimensiones sexuales: atracción romántica, atracción sexual y conducta sexual en el pasado, presente y futuro ideal, en una escala de 1 (solo hacia el otro sexo) a 5 (solo hacia el mismo sexo). Los resultados muestran una gran variedad de vivencias sexuales en las diferentes dimensiones evaluadas y cambios en función del momento temporal. Además, también se observó una relación positiva entre la edad y la atracción y conducta exclusivamente heterosexual. Estos resultados contribuyen al entendimiento de la sexualidad femenina y al diseño de programas de educación sexual para mujeres adultas.The social and scientifc invisibility of sexual diversity in adult women, as well as a reductionist way to understanding it, has led us to carry out a study with 523 adult women, with an average age of 38.52 years (SD = 6.83), of which 89.3% were considered heterosexual. Three sexual dimensions were evaluated: romantic attraction, sexual attraction and sexual behavior in the past, present and ideal future, on a scale of 1 (only towards the other sex) to 5 (only towards the same sex). The results show a great variety of sexual experiences in the different evaluated dimensions and changes depending on the temporal moment. In addition, a positive relationship between age and exclusively heterosexual attraction and behavior was also observed. These results contribute to the understanding of female sexuality and the design of sex education programs for adult women

Discriminación y actitudes hacia la diversidad afectivo-sexual: la experiencia de las mujeres

A pesar de los cambios socioculturales, las personas LGTBI todavía deben hacer frente a ciertas dificultades. El objetivo de este estudio es explorar la discriminación y las actitudes hacia la diversidad afectivo-sexual en mujeres. 145 mujeres de entre 17 y 43 años (M=29,63; DT=9,6), cumplimentaron un cuestionario ad hoc sobre discriminación y actitudes hacia el colectivo LGTBI. El 18,7% de las mujeres no heterosexuales ha sufrido discriminación por orientación/identidad sexual. Más mujeres no heterosexuales que heterosexuales (68% frente al 51,4%) han presenciado discriminación por estas cuestiones en su entorno. Encontramos ciertas actitudes negativas en ambos grupos, sobre todo en aquellos ítems relacionados con la expresión de género, la bisexualidad y transexualidad. Estos hallazgos indican la necesidad de educar en diversidad y visibilizar aquellos colectivos que son más excluidos para lograr la equidad y el respeto.Despite sociocultural changes, LGTBI people still have to face certain diffculties. The purpose of this study is to explore discrimination and attitudes towards sexual-affective diversity in women. 145 women between 17 and 43 years old (M = 29,63; SD = 9,6) completed an ad hoc questionnaire about discrimination and attitudes towards the LGTBI group. 18,7% of non-heterosexual women have suffered sexual orientation / identity discrimination. More non-heterosexual women than heterosexuals (68% vs. 51,4%) have witnessed discrimination by these issues in their environment. We found certain negative attitudes in both groups, especially in those items related to the expression of gender, bisexuality and transsexuality. These fndings indicate the need to educate in diversity and make visible those groups that are most excluded to achieve equity and respect

FORMACIÓN DE VALORES EN LA EDUCACIÓN INCLUSIVA EN LA UNIVERSIDAD CONTEMPORÁNEA

The university is the place where you learn the set of knowledges that will allow the future titled to pursue a profession or engage in the field of research. However, it is not so obvious that the university is a place where a set of ethical and citizen knowledge is learned. In addition, it is argued that one of the functions of university education is ethical and that it cannot be understood as a quality university education that does not systematically and rigorously incorporate situations of ethical learning and citizen training. This paper aims to explain some theoretical positions on the formation of values in inclusive education in contemporary university. The ethical role of education in today's society is given by human, personal and social training, which contributes to the ethical and moral optimization of future graduates. The formation of values in Inclusive Higher Education implies the commitment of the institution, the teachers and the entire educational community.La universidad es el lugar en el que se aprende el conjunto de saberes que permitirán al futuro titulado ejercer una profesión o dedicarse al ámbito de la investigación. Sin embargo, no resulta tan obvio que la universidad sea un lugar en el que se aprenda un conjunto de saberes éticos y ciudadanos. Además se sostiene que una de las funciones de la formación universitaria es de carácter ético y que no puede entenderse una formación universitaria de calidad que no incorpore de forma sistemática y rigurosa situaciones de aprendizaje ético y de formación ciudadana. Este trabajo tiene como objetivo explicar algunos posicionamientos teóricos sobre la formación de valores en la educación inclusiva en la universidad contemporánea. La función ética de la educación en la sociedad actual está dada por la formación humana, personal y social, que contribuya a la optimización ética y moral de los futuros egresados. La formación de valores en la Educación Superior Inclusiva supone el compromiso de la institución, de los profesores y de toda la comunidad educativa

Application of the Delphi Method for Content Validity Analysis of a Questionnaire to Determine the Risk Factors of the Chemsex

Chemsex is understood as 'the intentional use of stimulant drugs to have sex for an extended time among gay, bisexual, and other men who have sex with men'. It is a public health problem because of the increased incidence of cases and because of the consequences on the physical and mental health of those who practice it. Aim: This study aimed to analyze, with the help of the Delphi method, the content validity of a new instrument to assess the risk of behaviors associated with the chemsex phenomenon. Method: First, a bank of items identified from the literature was elaborated. Secondly, 50 experts with knowledge of the chemsex phenomenon at the national level were contacted. A Delphi group was formed with them to carry out two rounds of item evaluation. The linguistic evaluation (comprehension and appropriateness) was assessed using a Likert scale from 1 to 5 for each item. Items that did not reach a mean score of 4 were eliminated. Content assessment was calculated using each item's content validity index (CVI) and Aiken's V (VdA). A minimum CVI and VdA value of 0.6 was established to include the items in the questionnaire. Results: A total of 114 items were identified in the literature. In the first round of Delphi evaluation, 36 experts evaluated the items. A total of 58 items were eliminated for obtaining a CVI or VdA of less than 0.6, leaving 56 items. In a second Delphi round, 30 experts re-evaluated the 56 selected items, where 4 items were eliminated for being similar, and 10 items were also eliminated for not being relevant to the topic even though they had values higher than 0.6, leaving the scale finally composed of 52 items. Conclusion: A questionnaire has been designed to assess the risk of behaviors associated with the chemsex phenomenon. The items that make up the questionnaire have shown adequate content and linguistic validity. The Delphi method proved to be a helpful technique for the proposed objective

Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex

[Background] The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression.[Research Question] What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?[Study Design and Methods] We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time.[Results] The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039).[Interpretation] Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function.[Trial Registry] ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.govThis study was funded in part by an unrestricted grant from AstraZeneca, and also by the COPD Research Program of the Spanish Respiratory Society (PII de EPOC of SEPAR).Peer reviewe